Innate and Adaptive Immunity, Host-Microbe Interactions, and Biomedical Applications

Innate and Adaptive Immunity

Comparison of Innate and Adaptive Immunity

The immune system is divided into two main branches: innate immunity and adaptive immunity. Both work together to protect the body from pathogens, but they differ in specificity, memory, and response time.

• Innate Immunity: Non-specific, immediate response, no memory. Includes physical barriers, phagocytic cells, and chemical mediators.

• Adaptive Immunity: Specific to particular antigens, slower to respond initially, but generates immunological memory. Involves lymphocytes (T cells and B cells).

• Example: Skin and mucous membranes provide innate defense, while antibodies produced after vaccination are adaptive.

Normal Microbiota and the Immune System

Normal microbiota are the microorganisms that reside on and within the human body. They interact with the immune system in several ways:

• Compete with pathogens for nutrients and space (competitive exclusion).

• Stimulate the development and function of the immune system.

• Produce substances (e.g., bacteriocins) that inhibit pathogens.

First Line of Defense: Barriers

• Mechanical Barriers: Physical processes that remove microbes, such as cilia movement in the respiratory tract, flushing action of tears, saliva, and urine.

• Chemical Barriers: Substances that inhibit or destroy pathogens, including lysozyme in tears and saliva, acidic pH of the stomach, and fatty acids on the skin.

• Physical Barriers: Structural features like intact skin and mucous membranes that block pathogen entry.

Antimicrobial Peptides

Antimicrobial peptides (AMPs) are small proteins produced by host cells that disrupt microbial membranes, leading to cell death. Examples include defensins and cathelicidins.

Lymphoid Tissues

• Primary Lymphoid Tissues: Sites of lymphocyte development and maturation (bone marrow and thymus).

• Secondary Lymphoid Tissues: Sites where immune responses are initiated (lymph nodes, spleen, mucosa-associated lymphoid tissue).

Leukocytes (White Blood Cells)

Leukocytes are immune cells with various functions:

• Neutrophils: Phagocytosis and destruction of microbes.

• Eosinophils: Defense against parasites, involved in allergic responses.

• Basophils: Release histamine, involved in inflammation and allergies.

• Monocytes/Macrophages: Phagocytosis, antigen presentation.

• Lymphocytes: T cells (cell-mediated immunity), B cells (antibody production), and Natural Killer (NK) cells (kill infected or abnormal cells).

Cytokines

Cytokines are signaling proteins that regulate immune responses. Types include:

• Interleukins (ILs): Mediate communication between leukocytes.

• Interferons (IFNs): Antiviral responses, activate immune cells.

• Tumor Necrosis Factors (TNFs): Inflammation and apoptosis.

Interferons

Interferons are cytokines that interfere with viral replication and activate immune cells. They induce the expression of antiviral proteins in neighboring cells.

Iron-Binding Proteins

Proteins such as transferrin and lactoferrin sequester iron, limiting its availability to pathogens and inhibiting their growth.

Complement System

The complement system is a group of proteins that enhance immune responses. Activation leads to:

• Opsonization (enhanced phagocytosis)

• Inflammation

• Cell lysis via the membrane attack complex (MAC)

Inflammation

Inflammation is a protective response to infection or injury, characterized by:

• Redness (rubor)

• Heat (calor)

• Swelling (tumor)

• Pain (dolor)

These signs result from increased blood flow, vascular permeability, and migration of immune cells to the site of infection.

Fever

Fever is an elevated body temperature that enhances immune function and inhibits pathogen growth. It is triggered by pyrogens (e.g., IL-1, TNF-α).

Adaptive Immunity

Overview and Diagram of Adaptive Immunity

Adaptive immunity involves specific recognition of antigens and the generation of memory. It is mediated by T cells and B cells.

Antigens and Immunogenicity

• Antigen: Any substance that can be recognized by the immune system and elicit an immune response.

• Immunogenicity: The ability of an antigen to provoke an immune response.

Types of T Cells

• Cytotoxic T Cells (TC): Destroy infected or abnormal cells.

• Helper T Cells (TH): Activate other immune cells.

• Regulatory T Cells (TReg): Suppress immune responses to maintain tolerance.

Self-Tolerance Screening

Mechanisms that prevent the immune system from attacking self-antigens, including clonal deletion and anergy.

Comparison of T Cells and B Cells

• T Cells: Mediate cellular immunity, recognize antigens presented by MHC molecules.

• B Cells: Produce antibodies, recognize free antigens.

Major Histocompatibility Complexes (MHCs)

• MHC I: Present on all nucleated cells, present intracellular antigens to CD8+ T cells.

• MHC II: Present on antigen-presenting cells, present extracellular antigens to CD4+ T cells.

Antigen Presentation

• Intracellular Antigen Presentation: Endogenous antigens are processed and presented by MHC I to cytotoxic T cells.

• Extracellular Antigen Presentation: Exogenous antigens are processed and presented by MHC II to helper T cells.

T Cell Activation, Proliferation, and Differentiation

T cells are activated by antigen presentation, then proliferate and differentiate into effector and memory cells.

Cytotoxic T Cell Action

Cytotoxic T cells induce apoptosis in infected cells by releasing perforin and granzymes.

B Cell Activation

• T-Dependent Antigens: Require T cell help for B cell activation.

• T-Independent Antigens: Can activate B cells without T cell help.

B cells proliferate and differentiate into plasma cells (antibody producers) and memory B cells.

Antibody Functions and Structure

• Neutralization: Block pathogen binding.

• Opsonization: Enhance phagocytosis.

• Complement Activation: Trigger complement cascade.

Antibodies have a Y-shaped structure with variable (antigen-binding) and constant regions.

Antibody Types

• IgG: Most abundant, crosses placenta.

• IgM: First produced, pentameric.

• IgA: Found in mucosal areas.

• IgE: Involved in allergies and parasitic infections.

• IgD: Functions mainly as a B cell receptor.

Immunological Memory

Memory cells enable a faster and stronger response upon re-exposure to the same antigen.

Categories of Humoral Immunity

• Natural Active: Infection

• Natural Passive: Maternal antibodies

• Artificial Active: Vaccination

• Artificial Passive: Antibody therapy

Immunodeficiencies and Autoimmunity

• Primary Immunodeficiencies: Genetic defects affecting immune function.

• Secondary Immunodeficiencies: Acquired due to external factors (e.g., HIV, chemotherapy).

• Autoimmunity: Immune response against self-antigens.

Biomedical Applications: Vaccines and Diagnostics

Smallpox Eradication

Smallpox was eradicated through global vaccination campaigns, effective surveillance, and the absence of animal reservoirs.

Jenner’s Vaccination and the Term "Vaccine"

Edward Jenner used cowpox to protect against smallpox, coining the term "vaccine" from vacca (Latin for cow).

Herd Immunity

When a high proportion of a population is immune, the spread of infectious disease is limited, protecting those who are not immune.

Vaccine Categories

Type	Example	Benefits	Risks
Live Attenuated	MMR, Varicella	Strong, long-lasting immunity	Risk in immunocompromised
Inactivated	Polio (IPV)	Safe for most people	Weaker immunity, boosters needed
Subunit	Hepatitis B	Very safe	May require adjuvants
Toxoid	Tetanus	Targets toxins	Boosters required
Conjugate	Hib	Effective in young children	Cost

Agglutination Reactions and Blood Typing

Agglutination is the clumping of particles, used in blood typing and pathogen detection.

ELISAs (Enzyme-Linked Immunosorbent Assays)

• Direct ELISA: Detects antigens using labeled antibodies.

• Indirect ELISA: Detects antibodies using a secondary labeled antibody.

• Sandwich ELISA: Captures antigen between two antibodies.

Western Blotting

Technique to detect specific proteins using antibodies after separation by gel electrophoresis.

Host-Microbe Interactions and Pathogenesis

Tropism

Tropism refers to the specificity of a pathogen for a particular host tissue, determined by host receptors and pathogen factors.

Virulence Factors

Virulence factors are molecules that enhance a pathogen's ability to cause disease, such as toxins, adhesins, and enzymes.

ID50 and LD50

• ID50: Infectious dose for 50% of the population.

• LD50: Lethal dose for 50% of the population.

Basic Reproduction Number (R0)

R0 is the average number of secondary infections produced by one infected individual in a susceptible population.

Endotoxins and Exotoxins

• Endotoxin: Lipopolysaccharide (LPS) from Gram-negative bacteria, causes systemic effects.

• Exotoxins: Proteins secreted by bacteria, highly specific and potent.

Steps to Infection

1. Entry

2. Adhesion

3. Invasion

4. Multiplication

5. Exit

Portals of Entry and Exit

• Entry: Skin, respiratory tract, gastrointestinal tract, urogenital tract.

• Exit: Same as entry or via secretions, excretions, or blood.

Adhesion Factors

Structures or molecules (e.g., fimbriae, adhesins) that allow pathogens to attach to host cells.

Biofilm and Quorum Sensing

• Biofilm: Community of microorganisms encased in a protective matrix.

• Quorum Sensing: Cell-to-cell communication to coordinate gene expression.

Invasins

Enzymes or proteins that facilitate pathogen entry and spread within host tissues.

Immune Evasion Mechanisms

• Antigenic variation

• Inhibition of phagocytosis

• Destruction of immune cells

Transmission Modes and Precautions

Mode	Description	Precautions
Contact	Direct or indirect physical contact	Hand hygiene, gloves
Droplet	Large respiratory droplets	Masks, distance
Airborne	Small particles suspended in air	N95 respirators, negative pressure rooms